Association Between HbA1c Variability and Risk of Microvascular Complications in Adolescents With Type 1 Diabetes

J Clin Endocrinol Metab. 2016 Sep;101(9):3257-63. doi: 10.1210/jc.2015-3604. Epub 2016 May 17.


Context: There is a paucity of data regarding the association between glycosylated hemoglobin (HbA1c) variability and risk of microvascular complications in adolescents with type 1 diabetes (T1D).

Objective: To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D.

Design: Prospective cohort study from 1990 to 2014 (median follow-up, 8.1 y).

Setting: Tertiary pediatric hospital.

Participants: A total of 1706 adolescents (aged 12-20 minimum diabetes duration 5 y) with median age of 15.9 years (interquartile range, 14.3-17.5) and diabetes duration of 8.1 years (6.3-10.8).

Main outcome measures: Glycemic variability was computed as the SD of all HbA1c measurements (SD-HbA1c) after diagnosis. Retinopathy was detected using 7-field fundal photography, renal function assessed using albumin excretion rate, peripheral neuropathy detected using thermal and vibration threshold testing, and cardiac autonomic neuropathy (CAN) detected using time- and frequency-domain analyses of electrocardiogram recordings. Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability, after adjusting for known risk factors, including HbA1c, diabetes duration, blood pressure, and lipids.

Results: In multivariable analysis, SD-HbA1c was associated with early retinopathy (odds ratio [OR] 1.32; 95% confidence interval, 1.00-1.73), albuminuria (OR 1.81; 1.04-3.14), increased log10 albumin excretion rate (OR 1.10; 1.05-1.15) and CAN (OR 2.28; 1.23-4.21) but not peripheral neuropathy.

Conclusions: Greater HbA1c variability predicts retinopathy, early nephropathy, and CAN, in addition to established risk factors, in adolescents with T1D. Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Albuminuria / etiology*
  • Albuminuria / metabolism
  • Albuminuria / pathology
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Child
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / pathology
  • Diabetic Retinopathy / etiology*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Longitudinal Studies
  • Male
  • Prognosis
  • Prospective Studies
  • Young Adult


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human